{"title":"视网膜内皮细胞中微rna介导的Ets1抑制：非增生性糖尿病视网膜病变中一种新的抗血管生成机制。","authors":"Jianyu Zhao, Zewen Sun, Zimeng Li, Mengyu Xu, Aowen Tian, Zhengwen An, Wenbo Guo, Chang He, Ying Dong, Jianping Wen, Jianli Yang, Qing Wang, Peng Chen","doi":"10.1111/dom.16182","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).</p><p><strong>Materials and methods: </strong>This study employed a case-control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single-cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.</p><p><strong>Results: </strong>We identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto-oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single-cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin-1 and phosphoinositide 3-kinase-Akt (PI3K-Akt) signalling pathways, indicating an anti-angiogenic mechanism in NPDR.</p><p><strong>Conclusions: </strong>The identification of a novel microRNA involved in the anti-angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina-specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MicroRNA-mediated Ets1 repression in retinal endothelial cells: A novel anti-angiogenic mechanism in nonproliferative diabetic retinopathy.\",\"authors\":\"Jianyu Zhao, Zewen Sun, Zimeng Li, Mengyu Xu, Aowen Tian, Zhengwen An, Wenbo Guo, Chang He, Ying Dong, Jianping Wen, Jianli Yang, Qing Wang, Peng Chen\",\"doi\":\"10.1111/dom.16182\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).</p><p><strong>Materials and methods: </strong>This study employed a case-control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single-cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.</p><p><strong>Results: </strong>We identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto-oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single-cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin-1 and phosphoinositide 3-kinase-Akt (PI3K-Akt) signalling pathways, indicating an anti-angiogenic mechanism in NPDR.</p><p><strong>Conclusions: </strong>The identification of a novel microRNA involved in the anti-angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina-specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-01-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.16182\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.16182","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
MicroRNA-mediated Ets1 repression in retinal endothelial cells: A novel anti-angiogenic mechanism in nonproliferative diabetic retinopathy.
Aims: This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).
Materials and methods: This study employed a case-control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single-cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.
Results: We identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto-oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single-cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin-1 and phosphoinositide 3-kinase-Akt (PI3K-Akt) signalling pathways, indicating an anti-angiogenic mechanism in NPDR.
Conclusions: The identification of a novel microRNA involved in the anti-angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina-specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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